Abstract

BACKGROUND: ZW10 binding factor (ZWINT) has been reported to be upregulated in various human cancers and predict worse survival. However, the expression profile, clinical significance, and biological role of ZWINT remains unclear in breast cancer.

MATERIAL AND METHODS: In this study, we investigated messenger RNA (mRNA) and protein expression levels of ZWINT in breast cancer tissues, and the prognostic value of ZWINT protein expression was validated in a cohort of breast cancer patients using immunohistochemistry analysis. Then, different bioinformatic analyses were combined to explore the potential cancer-related hallmark underlying ZWINT in breast cancer, and a series of experiments in vitro were performed to reveal the oncogenic role of ZWINT in breast cancer.

RESULTS: Significant upregulation of ZWINT was observed in breast cancer tissues compared to normal and para-tumor tissues and upregulation of ZWINT predicts poor prognosis in breast cancer patients. Additionally, ZWINT could promote breast cancer proliferation via cell cycle regulation, especially by influencing the expression of some critical cell cycle regulators involved in G1 phase and G1/S transition. Finally, miR-204 was identified as a tumor suppressor microRNA which directly targets a specific site in 3’-UTR of ZWINT.

CONCLUSIONS: Overall, our results indicated that miR-204/ZWINT/cell cycle process might play an important role in breast cancer progression.

Keywords: Breast Neoplasms, Cell Cycle, Cell Proliferation, 3' Untranslated Regions, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Immunohistochemistry, Intracellular Signaling Peptides and Proteins, MicroRNAs, Nuclear Proteins, Prognosis, Survival Analysis, Up-Regulation